Variable phenotype in 17q12 microdeletions: Clinical and molecularcharacterization of a new case

Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutationsof this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinaryalterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer–Rokitansky–Küster–Hauser Syndrome (MRKH, OMIM277000) in females and, recently,were associatedwith intellectual disability,autistic features, cerebral anomaly and facial dysmorphisms.In this report, we describe a boywith a deletion in 17q12 region detected by SNP array, encompassing the HNF1Bgene, that showed dysmorphic features, intellectual disability (ID), serious speech delay and autistic features. Inaddition, obesity was observed. In order to study the parental origin of the rearrangement, we analyzed selectedSNPs in the deleted area in the patient and his parents, showing Mendelian incompatibilities suggesting a denovo deletion on the chromosome of maternal origin.Our case confirms the incomplete penetrance and variable expressivity of this deletion, its complex clinical variability,and strengthens the evidence that ID and stereotyped behaviors may be part of the phenotypic spectrumcharacterizing the affected patients. Also, it is useful to further delineate the phenotypes associated to the deletionbeing the first case in which obesity has been documented. We present a genotype–phenotype correlationdiscussing the possible role of some genes, encompassed by the deletion, in the etiology of the observedphenotypes.